In women with large and pendulous breasts postoperative radiotherapy in the supine position could represent a technical challenge because of the resulting dose inhomogeneity and the large amount of lung and heart receiving a high percentage of the prescribed dose. Breast-conserving surgery is therefore relatively contraindicated in these patients. Alternative positions for radiation therapy treatment have been proposed, and prone breast irradiation in particular has been recognized as a useful alternative to conventional treatment in the supine position. We report the case of a large-breasted patient treated in prone position in our radiation therapy division.